The present invention relates to an in vitro method for the diagnosis of multiple sclerosis and/or the susceptibility to multiple sclerosis comprising the steps of a) obtaining a biological sample; and b) detecting and/or measuring the increase, decrease and or absence of (a) specific marker gene(s) as disclosed herein. Furthermore, screening methods relating to inhibitors, activators, antagonists as well as agonists of the specific marker genes disclosed herein are provided. In addition pharmaceutical and diagnostic compositions are disclosed.
Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS. It is characterized by focal inflammation, demyelination and a variable degree of axonal loss and neuronal damage. Genomic analysis indicates that susceptibility for MS is related to several not yet identified genes. Incomplete penetrance of presumed MS susceptibility genes and genetic heterogeneity have prevented to define any specific markers for the diagnosis and the course of MS.
Brain tissue destruction occurs very early in the course of disease, when the damage is still clinically silent. Therefore, early diagnostic markers are needed as well as predictive markers for relapses to design the treatment according to disease activity. Because of the immunological characteristics of the disease several attempts to define immunological parameters for MS have been made. Blood brain barrier (BBB) breakdown and invasion of T cells into CNS are the early events of MS pathogenesis. There is an increasing body of evidence that interaction of various molecules are involved in the transendothelial migration of immune cells. These molecules comprise adhesion molecules, matrix metalloproteinases (MMPs), cytokines and chemokines. Magnetic resonance imaging (MRI) has provided the possibility to examine inflammatory activity and axonal alterations in CNS in vivo.
Several studies have shown that increase of MMP-9 in serum and cerebrospinal fluid (CSF) is correlated with disease course and with new gadolinium-enhancing lesions measured with MRI. The activity of MMPs is strictly controlled by endogenous tissue inhibitors of metalloproteinases (TIMPs). In fact, it has been demonstrated that increased MMP-9 and decreased TIMP1 levels are risk factors for formation of new gadolinium-enhancing lesions.
Whereas the above discussed two proteins are known to increase the risk of gadolinium-enhanced lesions when increased or decreased, respectively, there is still a need for specific means and methods for safe and reliable diagnosis of multiple sclerosis as well as for the development of effective means of therapeutic intervention in said chronic disorder. Therefore, the technical problem underlying the present invention was to provide for diagnostic markers as well as for therapeutic targets for multiple sclerosis.